The overall goal of our Program is to conduct research on the causes, prevention, and therapy of gastrointestinal (GI) cancers. We aim to have a strong translational component to our research that is enhanced by a close integration of the basic sciences with clinical and epidemiological research. With respect to etiological research, primary areas of interest include: a) assessing the roles of putative candidate genes, such as NAT 1 and 2 in colorectal cancer; b) studying prevalence and determinants of epigenetic events, such as hypermethylation of the estrogen receptor5 gene promoter, in colorectal tumor samples; c) characterizing population-based parameters for genes already accepted as causes of these cancers such as the mismatch repair genes in colorectal cancer; and d) how environmental factors may interact with these genetic factors. With respect to clinical research, an emerging them in our Program is to identify and understand why cancer patients or subjects with selected precursor lesions, such as Barrett's esophagus or colorectal polyps, have differential responses to therapeutic interventions. Increasingly, we are using molecular markers to develop a profile of patients who do or do not respond to a given therapy. This type of research involves a close collaboration between molecular biologists, clinicians, and epidemiologists. It has obvious and strong translational potential, since one goal, already being realized in some of our management of patients with Barrett's esophagus, is to tailor a given intervention to a given patient based on their likelihood of responding. In addition, we have strength in hepatitis research and hepatology, with four clinical research centers at USC (Hepatitis, Hepatitis C Virus, Alcohol, NIDDK). Given this existing expertise, we believe we have the potential for an active research program in liver cancer, and have established an infrastructure with monthly meetings to develop a research program in this area. To further enhance our already substantial research program in GI cancer, we are focusing on two near-term goals: 1) even better integration across the basic, clinical, and population-based sciences, and 2) strengthening our capabilities to apply high volume molecular technologies to ongoing and planned studies. Members of the GI Program currently have over $10,000,0000 in research support.